The goals of this study are the design, fabrication and initial in vitro and in vivo testing of a system for ablation (destruction) of pancreatic cancers, using high- intensity ultrasound to ablate via thermal heating effect, which will be monitored using MRTI (magnetic resonance thermal imaging). Heating of pancreatic cancers will ultimately be performed by insertion of MR-compatible ultrasonic delivery devices (called "applicators") into pancreatic cancers using endoscopic ultrasound (EUS) guidance. Following insertion of applicators into pancreatic cancers, patients will have the EUS endoscope removed, leaving MR-compatible applicators in place within the pancreatic tumor. These applicators will consist of several independently controlled high-output transducers capable of heating targeted regions of pancreatic cancer in a 3D conformal manner. The ultimate goal will be to treat all regions of pancreatic cancer to an ablative temperature in excess of 50 degrees centigrade, using MRTI to assure complete treatment, while sparing adjacent structures such as bowel. In this proposal, initial design and the in vitro testing of appropriately designed applicators will be performed in the first year, followed by continued development and testing in a swine model in the second year. Both acute (immediate) and chronic (longer-term) histologic changes caused by the ablative procedure in swine pancreata will be assessed by histologic analysis of resected pancreatic tissue after the ablative procedure. By correlating histologic changes with pancreatic treatment temperature profiles, as documented by MRTI, it will be possible to assess the desired thermal requirements for effective pancreatic tissue ablation using these techniques. In addition to MRTI for thermal monitoring of pancreatic ablation, a number of advanced MR imaging techniques (T2-weighted, contrast-enhanced, MTC (magnetization transfer contrast) and DWI (diffusion-weighted imaging) will be used to image the pancreas after the ablation procedure, in order to determine how effective these techniques are for discerning actual histologic changes following ablation. It is expected that these studies will result in a highly effective new technique for local ablation of pancreatic cancer with minimal side effects, providing an entirely new tool for cure or useful palliation of this disease. PUBLIC HEALTH RELEVANCE: Cancer of the pancreas is a common and highly malignant form of cancer that is the fourth leading cause of cancer death in the USA, but there are really no very good treatment methods. We propose the development of an image-guided minimally invasive technique to completely destroy pancreatic cancers while preserving normal tissues. If successful, the technique could be of great importance in providing meaningful treatment for a devastating disease for which there is no current effective treatment.